Urinary tract stone disease is a common human malady. The vast majority of stones formed in the urinary space are mineralized with calcium salts. Meyer et al., Invest. Urol., Vol. 13, pp. 36-39 (1975); Coe et al., Kidney Int., Vol. 38, pp. 625-631 (1990). Although normal urine is frequently supersaturated with respect to calcium oxalate, inhibitors are thought to protect most humans from the formation of stones. Nakagawa et al., J. Biol. Chem., Vol. 258, pp. 12594-12600 (1983). The most abundant protein in normal urine, Tamm-Horsfall protein (TH), Tamm et al., Proc. Soc. Exp. Biol. Med., Vol. 74, pp. 108-114 (1950), however, has been found to be inactive as an inhibitor of crystal growth, Worcester et al., Am. J. Physiol., 255, F1197-F1205 (1988), and attempts to identify proteins or other factors that fill this role have heretofore been only partially successful.
The discovery of factors present in urine responsible for preventing the formation of kidney stones would have potential therapeutic and diagnostic benefit to those suffering from such afflictions. The present invention is directed to addressing these, as well as other, important needs.